FAR2

Chr 12

fatty acyl-CoA reductase 2

Also known as: HEL-S-81, MLSTD1, SDR10E2

The FAR2 protein is a peroxisomal reductase that catalyzes the reduction of fatty acyl-CoA to fatty alcohols, which are essential substrates for ether lipid and plasmalogen synthesis. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and hearing loss, typically presenting in early childhood. This gene shows moderate constraint against loss-of-function variants, suggesting intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
32
P/LP submissions
0%
P/LP missense
0.43
LOEUF
DN
Mechanism· predicted
Clinical SummaryFAR2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 66 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.560
Z-score 3.62
OE 0.21 (0.110.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.70Z-score
OE missense 0.72 (0.640.81)
210 obs / 291.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.110.43)
00.351.4
Missense OE0.72 (0.640.81)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 5 / 24.2Missense obs/exp: 210 / 291.6Syn Z: -0.41
DN
0.6842th %ile
GOF
0.5269th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

120 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic2
VUS66
Likely Benign1
Benign3
30
Pathogenic
2
Likely Pathogenic
66
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
2
0
2
VUS
0
59
7
0
66
Likely Benign
0
1
0
0
1
Benign
0
0
2
1
3
Total060411102

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FAR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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